title: Effect of starvation and diet composition on two pathways of L-serine metabolism in isolated rat hepatocytes.
abstract: This study examined the effects of starvation and of feeding to rats diets that contain varying protein, carbohydrate and fat levels on serine metabolism in isolated hepatocytes. The conversion of [14C]serine and [14C]lactate to 14CO2 and [14C]glucose was measured in the presence and absence of 5 mM quinolinic acid (QA) or 1 mM 3-mercaptopicolinic acid (MPA), inhibitors of phosphoenolpyruvate carboxykinase. Inclusion of MPA eliminated the contribution of the serine dehydratase-mediated pathway of serine metabolism to glucose production, allowing estimation of serine aminotransferase-mediated metabolism. Addition of MPA reduced [14C]glucose formation from [14C]serine to between 3 and 47% of control values in all dietary treatments. Addition of 10 mM threonine or 10 mM pyruvate depressed [14C]glucose production in hepatocytes from the groups fed 80% protein. Differences in serine metabolism were observed within each protein group, depending on the carbohydrate and fat ratio of the diet. These results suggest the following: 1) MPA is a more potent gluconeogenic inhibitor than QA, permitting estimation of relative flux through two pathways of serine metabolism; 2) serine metabolism occurs primarily via serine dehydratase, although the contribution of serine aminotransferase varies depending upon the nutritional state of the rat, and 3) changing a single dietary component at the expense of another may mask the intricacies of metabolic homeostasis.
mesh_terms: D000818:Animals; D004032:Diet; D005943:Gluconeogenesis; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D010848:Picolinic Acids / Q000494:pharmacology; D011805:Quinolinic Acids / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012694:Serine / Q000378:metabolism*; D013217:Starvation / Q000378:metabolism*
chemical_list: D007773:Lactates; D010848:Picolinic Acids; D011805:Quinolinic Acids; D019344:Lactic Acid; D012694:Serine; C008363:3-mercaptopicolinic acid